Alonso 2005b.

Methods	Randomized controlled trial Generation of allocation sequence: computer generated in blocks of 6 Allocation concealment: central randomization was done at GlaxoSmithKline and the code released to the investigators after completion of follow up; opaque and masked coded syringes were used Blinding: investigator, participants, and outcome assessors blinded for first 6 months; investigators were not blinded during next 12 months Inclusion of all randomized participants: 383/417 (91.8%) of those randomized received 3 doses; 299/417 (71.7%) completed 6 months follow up (78.1% of those who received 3 doses); 352 entered single‐blind phase of whom 320 (90.9%) completed follow up Length of follow up: 18 months after third dose
Participants	Number: 417 children Inclusion criteria: age 1 to 4 years; resident in study area; full Expanded Programme of Immunization (EPI) immunization; parent's consent Exclusion criteria: history of allergic disease; packed cell volume ≤ 25%; weight for height ≤ 3 Z score; clinically significant chronic or acute disease; abnormal haematology or biochemistry variables
Interventions	1. RTS,S vaccine: 3 doses, 25 µg in 250 µL AS02A adjuvant, intramuscularly in deltoid (alternating arms) at 0, 1, and 2 months 2. 7‐valent pneumococcal conjugate vaccine (< 24‐months old; doses 1 and 3) plus Hib vaccine (dose 2) or hepatitis B vaccine (> 24‐months old; 3 doses) 4 weeks before start of surveillance, presumptive treatment with amodiaquine and sulfadoxine‐pyrimethamine was given; those children positive 2 weeks later were treated with second‐line drug and excluded from follow up
Outcomes	1. Time to first infection with Plasmodium falciparum malaria (case definition: presenting with temperature > 37.5 °C and parasitaemia > 2500/µL) 2. Clinical episodes of malaria 3. Malaria needing admission (P. falciparum sole cause of illness or important contributing factor) 4. All‐cause admission 5. Severe malaria (derived from World Health Organization definition: asexual P. falciparum parasitaemia; no other more probable cause of illness; plus composite of severe malaria anaemia (packed cell volume < 5%), cerebral malaria (Blantyre coma score < 2), and severe disease of other body systems (multiple seizures, prostration, hypoglycaemia, clinically suspected acidosis, or circulatory collapse) 6. Prevalence of parasitaemia 7. Prevalence of anaemia (packed cell volume < 25%) 8. Geometric mean parasite density in first clinical episode 9. Geometric mean parasite density in parasitaemic children at 6.5 months 10. Geometric mean titre to CS protein and hepatitis B surface antigen (HBsAg) 11. Seropositivity for anti‐CS antibody (> 0.5 international units/mL) and anti‐hepatitis B surface antigen (HBsAg) antibody (≥ 10 international units/mL) 12. Adverse events
Notes	Location: Ilha Josina, a lowland area 55 km north of Manhica, Mozambique with pronounced seasonality of transmission and more intense transmission than in Manhica Method of surveillance: active surveillance for infection by morbidity questionnaire, axillary temperature, and blood slides at home visits starting 2 weeks after dose 3, every 2 weeks for 2.5 months then monthly for 2 months; observation for 1 h after vaccination and once/day at home for 3 days after each dose for adverse events; complete blood count done 1 month after dose 3; creatinine, alanine aminotransferase (ALT), and bilirubin at months 1 and 6.5 after dose 3; cross‐sectional surveys with blood slide and axillary temperature taken at 6.5 months and 18 months after dose 3 This trial reported in same publication as Alonso 2005a